Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• explanation for these average yields could be the occurrence upon the base reaction with compound 47 of cis and trans conformations of the nitrosoacrylate. The cis one would be susceptible to undergo an immediate [2 + 4] cycloaddition with the furan whereas the trans form would not, and since the

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• suitable method for the binding mode of compounds in the rhAChE binding site. The docked conformations of donepezil and the synthesized compounds are shown in Figure 2. All docked compounds were located similar to donepezil in the binding pocket. The benzylpyridinium moiety was bound close to the CT and

• interaction to Trp86 in the CAS. Their conformations were slightly shifted up from Trp86 to form stronger a H-bond interaction between the 2-fluoro-substituent and a hydrogen atom of the β-carbon, thereby causing the slight shift of the remaining parts of the structures. For instance, the methoxy group of the

• -substituents, compound 9a does not form a H-bond interaction to Trp86, which explains the lower activity of compound 9a compared with compound 9h. For compounds 4a (Figure 3a) and 10a (Figure 3g), the docked conformations were partially different from the other compounds. In the case of 4a, having no methoxy

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• determinations were made on the possible major conformations, based upon those previously defined in reference [20]. Three distinct conformations (saddle, cone and 1,2-alternate) shown in Figure 2, were generated. Significantly, whereas for 3 which was based upon its X-ray structure, a partial cone conformer

• columnar arrays [17]. In this type of array the host molecules which are in 1,3-alternate conformations align in a “head-to-tail” fashion with the C60 molecules able to be accommodated within the opposite clefts. Furthermore, within such an arrangement, in addition to the “face-to-face” π–π interactions

• for the three different conformations of 5. Supporting Information Supporting Information File 355: Experimental determination of binding constants and DFT calculations. Supporting Information File 356: MOL files. Acknowledgements This project was supported by King Saud University, Deanship of

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• , those conformations are within 10 kJ/mol range of each other. However, only one of those conformations shows the required short distance between 14-H and 3-CH3, making the configuration (2R,3S,14R) probable for diastereomer 18. In the preferred conformation of 18, all non-sp3-hybridized carbon atoms of

• -containing 8 adopts two distinct major conformations in CDCl3, whereas diastereomeric diols 18 and 19 prefer only one, which were elucidated by NOESY spectroscopy. In upcoming studies we will address the synthesis of systems that contain a cyclohexene ring keeping the sp2–sp2 bridge of the product from the

• benzene partial structure. Preferred conformations of diastereomeric diols 18 and 19 including decisive NOESY correlations. Access to ketoester 14 that did not cyclize to the ethyl vinyl ether under McMurry conditions. Synthesis of the 1,3-cyclohexadiene-containing eunicellane-type [8.4.0]bicycle 18 by

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• conformations of the 5’-azido compounds 7 and 2 as well as dC macrocycle 4 were investigated in solution. To this end, high resolution spectra (600 MHz NMR) were measured in DMSO-d6 and the population of S vs N conformers (Supporting Information File 1, Table S2) were calculated using the program PSEUROT

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• arrangement. Starting from the pre-assembled catenane, the axle molecule is threaded through the wheel and end-capped by a copper-catalyzed click reaction. A variety of different spectroscopic and electrochemical methods was applied to reveal the switching behavior of 24 and its stable co-conformations in

• motion, a circumrotation and a translational motion, must occur. The equilibrium between these two co-conformations of 242(●+) was determined to be approximately 1:1. Further oxidation drives the equilibrium completely to the side of the co-conformation in which both dihydroxynaphthalene units are

• ′-bipyridinium radical cation which forms a purple trisradical complex with the doubly reduced cyclobis(paraquat-p-phenylene). Electrochemical and several spectroscopic techniques showed that, overall, six stable oxidation states – each of them with a unique color – and three co-conformations are accessible in

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• different conformations adopted by the wheel are reported here. Upon threading hexahexyloxycalix[6]arene 1 with ammonium axles 2+ or 3+, bearing biphenyl or trifluoromethylbenzyl moieties, respectively, two atropoisomeric pseudorotaxanes were formed in which the calix[6]-wheel 1 adopts the 1,2,3-alternate

• and cone conformations. The interconversion between them cannot be obtained by simple rotation around the ArCH2Ar bonds of the calixarene wheel, which is blocked by the presence of the axle inside its cavity. Therefore, it can only be obtained through a mechanism of de-threading/re-threading of the

• catalysis [24]. The widespread use of the calixarene derivatives is due to their convenient synthesis and to their chemical and conformational versatility [25]. In fact, calixarene macrocycles present a conformational isomerism that in the case of calix[6]arenes gives rise to eight discrete conformations

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• sites and these two possible co-conformations are designated A and B in Figure 4a. The ethylene protons at the core of the bis(pyridinium)ethane motif, labelled s and t in A and s’ and t’ in B are clearly distinguishable and show that there is a 4:1 ratio of A:B indicating that the smaller DB24C8 ring

• crown resides solely on the bis(pyridinium)ethane site for [8DB24C8]6+ but, when the [2]catenane does not absorb in the UV–visible region yielding a colorless solution this means the crown ether must be shuttling (i.e., circumrotating) back and forth between the two co-conformations, A and B, of [8

• + can be protonated to yield [8-HDB24C8]7+ in two different co-conformations A and B. b) The partial 1H NMR spectrum (500 MHz, 298 K, CD3CN) of [8-HDB24C8]7+ shows key resonances for both co-conformations A (red) and B (blue). See Scheme 1 for labelling; atoms of co-conformer B are labelled with a prime

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• carbohydrate binding site. They are flexible and can be more distant to one another (“open gate”) or closer together (“closed gate”) [20]. Both conformations were considered for the docking studies. For each docked conformation, a scoring value is obtained that correlates with the affinity of the ligand to the

• carbohydrate binding site. A more negative value predicts better binding. Scores obtained for mannosides 3 and 4 suggest a high affinity for FimH, surpassing that of pNPMan 1 for both protein conformations tested (Table 1). (Diazirines cannot be tested in bacterial adhesion–inhibition assays due to their light

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• of a neighboring ‘arm’; (ii) H-bonds between arginine terminal N–H and C=O of the peptide bond of phenylalanine of an adjacent cyclic pentapeptide (see Supporting Information File 1), yielding adjacent cyclic pentapeptides in close proximity for a large set of conformations. This separation between

• this large molecule, the conformations reported here represent relaxed geometries showing possible intermolecular contacts between the cyclic pentapeptides. The analysis and visualization of MD simulations were carried out using DS BIOVIA and Chimera [84] software. Targeted multivalent phototherapeutic

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• (IEFPCM) and considering DMSO (ε = 46.826) as the solvent environment; the total electronic energies of the anti–anti conformations were taken as the reference value. Free energies of solvation (ΔG) of compounds 2a, 3, D-Cl and D-N

  NH were calculated at the M06-2X/def2-TZVP level of theory (solvent

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• electrostatic interactions, after which they tend to adopt helical conformations, which causes cell membrane permeabilization or even membrane disruption that may lead to necrosis [33]. These peptides may also be internalized into the cell, leading to the disruption of the mitochondrial membrane and causing

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• linearity of the technique and the comparable IR absorption cross section of all predicted dimer conformations (cf. Table 1 and Table S1, Supporting Information File 1): the global minimum structure and any other, higher lying isomers which are initially formed and impeded from relaxation to the global

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• binding behavior of ZB4 and lays the basis for the construction of stimuli-responsive materials with ZB4 as a major component. Keywords: conformations; host–guest chemistry; macrocycles; supramolecular chemistry; zorb[4]arene; Introduction Macrocyclic receptors are the principal workhorses used in

• solutions and the different conformations in the solid state may result from the packing of the different lower-rim alkyl groups. For the conformers with cavities (Scheme 1b), three out of the four have been predominantly selected by three different guests. For example, guests 2+ and 3+ induced conformers

• IV and III, respectively, to achieve optimal binding [37]. This has been unambiguously confirmed by X-ray single crystallography (Figure 1b and 1c). Guest 10+ is a strong binder and its induction on the conformations of ZB4 was further analyzed. The guest exchange in solution of 10+@ZB4 is fast

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• ; Introduction EPR spectroscopy is well established to study the structure and dynamics of nucleic acids [1][2][3][4][5][6][7][8]. Although the information attainable by EPR is less detailed when compared to NMR, it is often complementary. While local conformations are normally obtained from NMR data, EPR can

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• respect to the central benzene ring. In such twisted conformations there is a remarkable steric hindrance between the ortho hydrogen atoms of the central benzene ring and the ortho' hydrogen atoms of the peripheral aromatic units. These conformations are not favorable for a complexation of aromatic guests

• and the host–guest interactions must be able to equilibrate the previously described ortho–ortho' hindrance and to bring the aromatic rings of the caps to coplanar conformations. In this work, we decided to investigate a new cryptand in which this steric hindrance is removed. Thus, we changed the

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• can be reversed by the incorporation of azobenzene units in macrocyclic arrangements [15]. For example, the groups of Tamaoki [16] and Herges [17] reported azobenzophanes that isomerize thermally to their energetically lower Z-conformations from their corresponding higher energy E-isomers. Moreover

• are possible for the stabilization of Z-azobenzenes 4–7. To estimate the influences of those effects, a conformer distribution analysis was performed to identify low-lying conformations of the corresponding (Z)-azobenzenes. The energetically favored conformers found (within 1.5 kcal mol−1 for 4 and 5

• kcal mol−1 for 5–7, respectively, relative to the lowest energy conformer) were then re-optimized at the B3LYP/6-31G** [26][27][28][29] level of theory with and without D3(BJ) [30][31] dispersion correction (gas phase) (conformations of one enantiomer of each diastereomer of 4 were analyzed. The

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• reacted with several nucleophiles. These reactions afforded disubstituted piperidine derivatives with high diastereoselectivities and good to excellent yields. The conformations of the obtained N-acyliminium ions were studied by low temperature NMR analyses and DFT calculations and were found to be

• , and C6 were also performed. The conformations of C2 and C6 were similar to those of C1 and C5, respectively (C2: pseudo-equatorial, C6: pseudo-axial). Although the conformation of C4 could not be determined by the NMR analysis, the conformation is assumed to be similar to that of C3 (pseudo-equatorial

• ). First, ΔG of pseudo-equatorial and pseudo-axial conformations of C1 was calculated at the B3LYP/6-31G(d) level of theory. The pseudo-equatorial conformation of C1 was more stable than the pseudo-axial conformation by 1.27 kcal/mol. Similarly, DFT calculations of C3 and C5 were performed, and the results

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• conformations around the two respective torsion angles [37][38]. In this case, it is also highly probable that hydrogen bonding will reinforce these conformational preferences. Whilst it was not possible to isolate crystals of 3 that were suitable for X-ray analysis, it was possible to unambiguously establish

Correlation effects and many-body interactions in water clusters

• Andreas Heßelmann

Beilstein J. Org. Chem. 2018, 14, 979–991, doi:10.3762/bjoc.14.83

• essential to describe the structures of (H2O)2 and (H2O)3 in many different conformations [15]. A rather good correlation between the coupled-cluster energies and the force-field energies is found for the polarisable AMOEBA2003 [9][16] and TTM4-F [17] potentials both for the dimer and for the trimer. Both

• accounted for by the HF method, see also below. The dependence of the electrostatic and dispersion energy on the structure is highlighted in Figure 5 for three different conformations of the water dimer. These three structures have in common the distance of the oxygen atoms (2.98 Å in this example), but

• interaction strongly reduces by +6 kcal/mol, yet remains attractive having a magnitude of about −6 kcal/mol for the structures 2 and 3. The blue horizontal bars in Figure 6 show the energy levels of the corresponding three-body dispersion energy for the three conformations. As can be seen, it possesses just

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• cavity. One disordered hydroxy group in host A and two in host B illustrate both gauche–gauche and gauche–trans conformations pointing inwards and outwards the cavity. The β-CD dimers stack along c-axis, the angle between their approximate seven-fold axis and c-axis being 7.86°, and form layers along the

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• twisted phenyl–pyrimidine/phenyl–pyridine conformation (i.e., a larger dihedral angle) in CN-P3/CN-P2. All the DFT-optimized data were in perfect accordance with single crystal X-ray diffraction analyses. The results showed that the molecular conformations (twist angles in D-spacer-A diads) could be

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• conformations depending on conditions. Z-DNA, a GC-repeat rich, thermodynamically less preferred, left-handed helical conformation that is favored by cytosine methylation is known to form in vivo under negative supercoiling or high salt concentrations [64][65][66][67][68]. Circular dichroism is traditionally

• breathing. Moreover, the data demonstrated that the structural changes upon binding of TFAM near the transcription initiation site are the result of sequence-independent binding to DNA. The investigation establishes the potential of using base–base FRET for studying nucleic acid conformations in vital

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• , supported by computation, that this effect is due to reactive conformations in which the C–X bond is orthogonal to the carbonyl group for good orbital overlap being disfavoured in the case of fluoro ketones. Keywords: α-halogenated ketones; conformational analysis; reactivity; stereoelectronic effects

• variants. The energy minimum for α-fluoroacetophenone was displayed at an O=C–C–X dihedral angle of around 140° in the gas phase, whilst the chloro- and bromoacetophenones both showed minima around 110°. Highly polar conformations which place the C–X bond in the same plane as the carbonyl group were

• smaller dihedral angle preferred by the chlorinated derivative in the gas phase. Figure 3 compares the lowest energy conformations of α-fluoroacetophenone and α-chloroacetophenone in the polar solvent ethanol. Experimental work by Olivato amongst others supports these conformational preferences [11][12